A comprehensive study on machine learning models combining with oversampling for bronchopulmonary dysplasia-associated pulmonary hypertension in very preterm infants.

BACKGROUND: Bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) remains a devastating clinical complication seriously affecting the therapeutic outcome of preterm infants. Hence, early prevention and timely diagnosis prior to pathological change is the key to reducing morbidity and improving prognosis. Our primary objective is to utilize machine learning techniques to build predictive models that could accurately identify BPD infants at risk of developing PH. METHODS: The data utilized in this study were collected from neonatology departments of four tertiary-level hospitals in China. To address the issue of imbalanced data, oversampling algorithms synthetic minority over-sampling technique (SMOTE) was applied to improve the model. RESULTS: Seven hundred sixty one clinical records were collected in our study. Following data pre-processing and feature selection, 5 of the 46 features were used to build models, including duration of invasive respiratory support (day), the severity of BPD, ventilator-associated pneumonia, pulmonary hemorrhage, and early-onset PH. Four machine learning models were applied to predictive learning, and after comprehensive selection a model was ultimately selected. The model achieved 93.8% sensitivity, 85.0% accuracy, and 0.933 AUC. A score of the logistic regression formula greater than 0 was identified as a warning sign of BPD-PH. CONCLUSIONS: We comprehensively compared different machine learning models and ultimately obtained a good prognosis model which was sufficient to support pediatric clinicians to make early diagnosis and formulate a better treatment plan for pediatric patients with BPD-PH.

[LU Yonghui's clinical experience of hierachical acupuncture at acupoints of conception vessel in treatment of benign prostatic hyperplasia].

The paper introduces professor LU Yonghui 's academic thought and clinical experience in treating benign prostatic hyperplasia (BPH). It is believed that the pathogenesis of BPH includes retarded qi movement of triple energizers and dysfunction of the bladder in qi activity, resulting in impairment of water metabolism, and difficulty in micturition occurs. In treatment, acupuncture is delivered at the muscle region (membrane) of the body to promote qi circulation. The needles are inserted at the acupoints of conception vessel to different depths. The shallow insertion is operated at Qihai (CV 6) and Guanyuan (CV 4) to benefit qi movement of triple energizers, the moderate insertion is at Zhongji (CV 3), the front-mu point of the bladder, to benefit the intersections (membranes) of triple energizers, and the deep insertion is at Qugu (CV 2) to work at the internal organ, regulate qi, remove obstruction. As a result, the qi movement of triple energizers is improved, the function of the bladder in qi activity recovered, urination ameliorated and the retention of urine cured.

Design, synthesis and biological evaluation of novel 3C-like protease inhibitors as lead compounds against SARS-CoV-2.

Background: The epidemic caused by SARS-CoV-2 swept the world in 2019. The 3C-like protease (3CLpro) of SARS-CoV-2 plays a key role in viral replication, and its inhibition could inhibit viral replication. Materials & methods: The virtual screen based on receptor-ligand pharmacophore models and molecular docking were conducted to obtain the novel scaffolds of the 3CLpro. The molecular dynamics simulation was also carried out. All compounds were synthesized and evaluated in biochemical assays. Results: The compound C2 could inhibit 3CLpro with a 72% inhibitory rate at 10 µM. The covalent docking showed that C2 could form a covalent bond with the Cys145 in 3CLpro. Conclusion: C2 could be a potent lead compound of 3CLpro inhibitors against SARS-CoV-2.

[Box: see text].

Targeting the TGF-ß signaling pathway: an updated patent review (2021-present).

INTRODUCTION: The TGF-ß signaling pathway is a complex network that plays a crucial role in regulating essential biological functions and is implicated in the onset and progression of multiple diseases. This review highlights the recent advancements in developing inhibitors targeting the TGF-ß signaling pathway and their potential therapeutic applications in various diseases. AREA COVERED: The review discusses patents on active molecules related to the TGF-ß signaling pathway, focusing on three strategies: TGF-ß activity inhibition, blocking TGF-ß receptor binding, and disruption of the signaling pathway using small molecule inhibitors. Combination therapies and the development of fusion proteins targeting multiple pathways are also explored. The literature search was conducted using the Cortellis Drug Discovery Intelligence database, covering patents from 2021 onwards. EXPERT OPINION: The development of drugs targeting the TGF-ß signaling pathway has made significant progress in recent years. However, addressing challenges such as specificity, systemic toxicity, and patient selection is crucial for their successful clinical application. Targeting the TGF-ß signaling pathway holds promise as a promising approach for the treatment of various diseases.

Genome editing of FTR42 improves zebrafish survival against virus infection by enhancing IFN immunity.

The development of CRISPR-Cas9 technology introduces an efficient tool for precise engineering of fish genomes. With a short reproduction cycle, zebrafish infection mode can be referenced as antiviral breeding researches in aquaculture fish. Previously we identified a crucian carp-specific gene ftrca1 as an inhibitor of interferon response in vitro. Here, we demonstrate that genome editing of zebrafish ftr42, a homolog of ftrca1, generates a zebrafish mutant (ftr42lof/lof) with an improved resistance to SVCV infection. Zebrafish ftr42 acts as a virus-induced E3 ligase and downregulates IFN antiviral response by facilitating TBK1 protein degradation and also IRF7 mRNA decay. Genome editing results in loss of function of zebrafish ftr42, which enables zebrafish to have enhanced interferon response, thus improving zebrafish survival against virus infection. Our results suggest that fine-tuning fish IFN innate immunity through genome editing of negative regulators can genetically improve viral resistance in fish.

WP1066, a small molecule inhibitor of STAT3, chemosensitizes paclitaxel-resistant ovarian cancer cells to paclitaxel by simultaneously inhibiting the activity of STAT3 and the interaction of STAT3 with Stathmin.

Paclitaxel is widely used to treat cancer, however, drug resistance limits its clinical utility. STAT3 is constitutively activated in some cancers, and contributes to chemotherapy resistance. Currently, several STAT3 inhibitors including WP1066 are used in cancer clinical trials. However, whether WP1066 reverses paclitaxel resistance and the mechanismremains unknown. Here, we report that in contrast to paclitaxel-sensitive parental cells, the expressions of several pro-survival BCL2 family members such as BCL-2, BCL-XL and MCL-1 are higher in paclitaxel-resistant ovarian cancer cells. Meanwhile, STAT3 is constitutively activated while stathmin loses its activity in paclitaxel-resistant cells. Importantly, WP1066 amplifies the inhibition of cell proliferation, colony-forming ability and apoptosis of ovarian cancer cells induced by paclitaxel. Mechanistically, WP1066, on the one hand, interferes the STAT3/Stathmin interaction, causing unleash of STAT3/Stathmin from microtubule, thus destroying microtubule stability. This process results in reduction of Ac-α-tubulin, further causing MCL-1 reduction. On the other hand, WP1066 inhibits phosphorylation of STAT3 by JAK2, and blocks its nuclear translocation, therefore repressing the transcription of pro-survival targets such as BCL-2, BCL-XL and MCL-1. Finally, the two pathways jointly promote cell death. Our findings reveal a new mechanism wherein WP1066 reverses paclitaxel-resistance of ovarian cancer cells by dually inhibiting STAT3 activity and STAT3/Stathmin interaction, which may layfoundation for WP1066 combined with paclitaxel in treating paclitaxel-resistant ovarian cancer.

A zebrafish NLRX1 isoform downregulates fish IFN responses by targeting the adaptor STING.

In mammals, NLRX1 is a unique member of the nucleotide-binding domain and leucine-rich repeat (NLR) family showing an ability to negatively regulate IFN antiviral immunity. Intron-containing genes, including NLRX1, have more than one transcript due to alternative splicing; however, little is known about the function of its splicing variants. Here, we identified a transcript variant of NLRX1 in zebrafish (Danio rerio), termed NLRX1-tv4, as a negative regulator of fish IFN response. Zebrafish NLRX1-tv4 was slightly induced by viral infection, with an expression pattern similar to the full-length NLRX1. Despite the lack of an N-terminal domain that exists in the full-length NLRX1, overexpression of NLRX1-tv4 still impaired fish IFN antiviral response and promoted viral replication in fish cells, similar to the full-length NLRX1. Mechanistically, NLRX1-tv4 targeted STING for proteasome-dependent protein degradation by recruiting an E3 ubiquitin ligase RNF5 to drive the K48-linked ubiquitination, eventually downregulating the IFN antiviral response. Mapping of NLRX1-tv4 domains showed that its N-terminal and C-terminal regions exhibited a similar potential to inhibit STING-mediated IFN antiviral response. Our findings reveal that like the full-length NLRX1, zebrafish NLRX-tv4 functions as an inhibitor to shape fish IFN antiviral response.IMPORTANCEIn this study, we demonstrate that a transcript variant of zebrafish NLRX1, termed NLRX1-tv4, downregulates fish IFN response and promotes virus replication by targeting STING for protein degradation and impairing the interaction of STING and TBK1 and that its N- and C-terminus exhibit a similar inhibitory potential. Our results are helpful in clarifying the current contradictory understanding of structure and function of vertebrate NLRX1s.

An Anti-CD7 Antibody-Drug Conjugate Target Showing Potent Antitumor Activity for T-Lymphoblastic Leukemia (T-ALL).

Acute T-lymphoblastic leukemia (T-ALL) is a type of leukemia that can occur in both pediatric and adult populations. Compared to acute B-cell lymphoblastic leukemia (B-ALL), patients with T-cell T-ALL have a poorer therapeutic efficacy. In this study, a novel anti-CD7 antibody-drug conjugate (ADC, J87-Dxd) was successfully generated and used for T-ALL treatment. Firstly, to obtain anti-CD7 mAbs, we expressed and purified the CD7 protein extracellular domain. Utilizing hybridoma technology, we obtained three anti-CD7 mAbs (J87, G73 and A15) with a high affinity for CD7. Both the results of immunofluorescence and Biacore assay indicated that J87 (KD = 1.54 × 10-10 M) had the highest affinity among the three anti-CD7 mAbs. In addition, an internalization assay showed the internalization level of J87 to be higher than that of the other two mAbs. Next, we successfully generated the anti-CD7 ADC (J87-Dxd) by conjugating DXd to J87 via a cleavable maleimide-GGFG peptide linker. J87-Dxd also possessed the ability to recognize and bind CD7. Using J87-Dxd to treat T-ALL cells (Jurkat and CCRF-CEM), we observed that J87-Dxd bound to CD7 was internalized into T-ALL cells. Moreover, J87-Dxd treatment significantly induced the apoptosis of Jurkat and CCRF-CEM cells. The IC50 (half-maximal inhibitory concentration) value of J87-Dxd against CCRF-CEM obtained by CCK-8 assay was 6.3 nM. Finally, to assess the antitumor efficacy of a J87-Dxd in vivo, we established T-ALL mouse models and treated mice with J87-Dxd or J87. The results showed that on day 24 after tumor inoculation, all mice treated with J87 or PBS died, whereas the survival rate of mice treated with J87-Dxd was 80%. H&E staining showed no significant organic changes in the heart, liver, spleen, lungs and kidneys of all mice. In summary, we demonstrated that the novel anti-CD7 ADC (J87-Dxd) had a potent and selective effect against CD7-expressing T-All cells both in vitro and in vivo, and could thus be expected to be further developed as a new drug for the treatment of T-ALL or other CD7-expression tumors.

Dual-slab Yb:KGd(WO4)2 regenerative amplifier for spectral shaping and high-power output.

A high-power regenerative amplifier (RA) based on dual-slab Yb:KGd(WO4)2 (Yb:KGW) was demonstrated, which provided a maximum average power of 33.7 W at a repetition rate of 75-200 kHz before compression with a central wavelength of 1039 nm, corresponding to an optical-to-optical conversion efficiency of 51.4%. To the best of our knowledge, this is the highest average power from the Yb:KGW solid-state RA. The compressed pulse duration of 205 fs was realized under the maximum output power. By adjusting the gain of the crystals, respectively, the spectral shaping can be achieved. A combination spectrum with root-mean-square (RMS) bandwidth of 4.5 nm was generated with a central wavelength of 1035 nm at an output power of 20 W, the compressed pulse duration was 159 fs. Meanwhile, effective mitigation of thermal effects by dual-slab configuration guaranteed the nearly diffraction-limited beam quality: M x2 = 1.17 and M y2 = 1.20.

A study on fiber Bragg grating (FBG) strain sensor based on symmetrical lever structure.

Thin-walled structure deformation detection technology is one of the key technologies for structural health monitoring and fault diagnosis of high-end mechanical equipment. Aiming at the problem that the existing Fiber Bragg Grating (FBG) strain sensor is difficult to effectively measure the deformation of thin-walled structures, an FBG strain sensor based on a symmetrical lever structure is proposed. The sensitivity of the sensor is analyzed theoretically, and the sensor is simulated and analyzed by the SOLIDWORKS and Abaqus software, and then, the structural parameters are optimized. According to the simulation results, the sensor is developed and a strain testing system is set up to test the performance of the sensor. The results indicate that the sensor sensitivity is ∼6.6 pm/µÎµ, which is about 5.5 times that of bare FBG. Its strain measurement sensitivity and stability are much higher than those of bare FBG, thus meeting the strain detection requirements of thin-walled structural parts during deformation. Moreover, the linearity is more than 99%, which enables the accurate measurement of tiny strains caused by the deformation and reconstruction of the thin-walled structure by the strain sensor. The results of this study provide a reference for the development of like sensors and a further improvement in the sensitivity of the optic-fiber strain sensor.

Natural products for the treatment of neurodegenerative diseases.

BACKGROUND: Neurodegenerative diseases are among the most common diseases in older adults worldwide. Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most common neurodegenerative diseases, and are accompanied by cerebral cortical atrophy, neuronal loss, protein accumulation, and excessive accumulation of metal ions. Natural products exhibit outstanding performance in improving cerebral circulatory disorders, promoting cerebral haematoma absorption, repairing damaged nerve tissue, and improving damaged nerve function. In recent years, studies have shown that neuroinflammatory mechanisms and signalling pathways closely related to the occurrence and development of neurological diseases include microglial activation, nuclear factor-κB (NF-κB) pathway, mitogen activated protein kinases (MAPK) pathway, reactive oxygen pathway, nucleotide binding oligomerisation domain-like receptor protein3 (NLRP3) inflammasomes, toll-like receptor4 (TLR4) pathway, nuclear factor erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) pathway, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, and intestinal flora. Therefore, this study considered the mechanism of neurological diseases as the starting point to review the mechanism of action of natural products in the prevention and treatment of AD and PD in recent years to provide a theoretical basis for clinical prevention and treatment. AIM: Natural products are a promising source of novel lead structures that have long been used to treat various nervous system diseases. METHODOLOGY: This review collected literature on neurological diseases and natural products from 2012 to 2022, which were mainly searched through databases such as ScienceDirect, Springer, PubMed, SciFinder, China National Knowledge Infrastructure (CNKI), Wanfang, Google Scholar, and Baidu Academic. The following keywords were searched: neurological disorders, natural products, signalling pathway, mechanism of action. RESULTS: This review summarises the pathogenesis of degenerative neurological diseases, recent findings on natural products used in neurodegenerative diseases, and the molecular mechanisms underlying these effects.

[Exploration of the diagnosis and treatment for benign prostatic hyperplasia with acupuncture based on jingjin theory].

Benign prostatic hyperplasia is caused by kidney deficiency and impaired qi transformation of the urinary bladder and is manifested by the stagnation of essence chamber. Based on jingjin (muscle region of meridian, sinew/fascia) theory and taking the visceral membrane as the principal, acupuncture is delivered at sinew/fascia to promote qi circulation, resolve stasis and open the orifice. Guided by CT, the needle is inserted at Zhongji (CV 3), the front-mu point of the urinary bladder, and then goes to the prostatic capsule, meaning "the disease of zang organ is treated by needling the front-mu point". In treatment of benign prostatic hyperplasia, this acupuncture therapy stimulates the different layers of fascia, by which, the defensive qi on the exterior is regulated and "essence orifice" in the interior is adjusted so that the urination can be promoted.

Idiopathic hypereosinophilic syndrome with hepatic sinusoidal obstruction syndrome: A case report and literature review.

BACKGROUND: Hypereosinophilic syndrome (HES) is classified as primary, secondary or idiopathic. Idiopathic HES (IHES) has a variable clinical presentation and may involve multiple organs causing severe damage. Hepatic sinusoidal obstruction syndrome (HSOS) is characterized by damage to the endothelial cells of the hepatic sinusoids of the hepatic venules, with occlusion of the hepatic venules, and hepatocyte necrosis. We report a case of IHES with HSOS of uncertain etiology. CASE SUMMARY: A 70-year-old male patient was admitted to our hospital with pruritus and a rash on the extremities for > 5 mo. He had previously undergone antiallergic treatment and herbal therapy in the local hospital, but the symptoms recurred. Relevant examinations were completed after admission. Bone marrow aspiration biopsy showed a significantly higher percentage of eosinophils (23%) with approximately normal morphology. Ultrasound-guided hepatic aspiration biopsy indicated HSOS. Contrast-enhanced computed tomography (CT) of the upper abdomen showed hepatic venule congestion with hydrothorax and ascites. The patient was initially diagnosed with IHES and hepatic venule occlusion. Prednisone, low molecular weight heparin and ursodeoxycholic acid were given for treatment, followed by discontinuation of low molecular weight heparin due to ecchymosis. Routine blood tests, biochemical tests, and imaging such as enhanced CT of the upper abdomen and pelvis were reviewed regularly. CONCLUSION: Hypereosinophilia may play a facilitating role in the occurrence and development of HSOS.

Use of Patient-Reported Outcome Measures in Lower Extremity Research.

Background: A large number of patient reported outcome measures (PROMs) have been developed for specific lower extremity orthopaedic pathologies. However, a consensus as to which PROMs are recommended for use in evaluating treatment outcomes for patients with hip, knee, ankle and/or foot pathology based on the strength of their psychometric properties is lacking. Objective: To identify PROMs that are recommended in systematic reviews (SRs) for those with orthopaedic hip, knee, foot, and ankle pathologies or surgeries and identify if these PROMs are used in the literature. Study design: Umbrella Review. Methods: PubMed, Embase, Medline, Cochrane, CINAHL, SPORTDisucs and Scopus were searched for SRs through May 2022. A second search was done to count the use of PROMs in seven representative journals from January 2011 through May 2022.SRs that recommended the use of PROMs based on their psychometric properties were included in the first search. SRs or PROMs not available in the English were excluded. The second search included clinical research articles that utilized a PROM. Case reports, reviews, and basic science articles were excluded. Results: Nineteen SRs recommended 20 PROMs for 15 lower extremity orthopaedic pathologies or surgeries. These results identified consistency between recommended PROMs and utilization in clinical research for only two of the 15 lower extremity pathologies or surgeries. This included the use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Copenhagen Hip and Groin Outcome Score to assess outcomes (HAGOS) for those with knee osteoarthritis and groin pain, respectively. Conclusion: A discrepancy was found between the PROMs that were recommended by SRs and those used to assess clinical outcomes in published research. The results of this study will help to produce more uniformity with the use of PROMs that have the most appropriate psychometric properties when the reporting treatment outcomes for those with extremity pathologies. Level of evidence: 3a.

Cross-Culturally Adapted Versions of Patient Reported Outcome Measures for the Lower Extremity.

Background: A large number of patient reported outcome measures (PROMs) have been developed in the English language for various lower extremity orthopaedic pathologies. Twenty different PROMs were recommended for 15 specific musculoskeletal lower extremity pathologies or surgeries. However, the availability of cross-culturally adapted versions of these recommended PROMs is unknown. Purpose: The purpose of this study was to identify the cross-culturally adapted versions of recommended PROMs for individuals experiencing orthopedic lower extremity pathologies or undergoing surgeries, and to identify the psychometric evidence that supports their utilization. Study design: Literature Review. Methods: PubMed, Embase, Medline, Cochrane, CINAHL, SPORTDisucs and Scopus were searched for cross-culturally adapted translated studies through May 2022. The search strategy included the names of the 20 recommended PROMs from previous umbrella review along with the following terms: reliability, validity, responsiveness, psychometric properties and cross-cultural adaptation. Studies that presented a non-English language version of the PROM with evidence in at least one psychometric property to support its use were included. Two authors independently evaluated the studies for inclusion and independently extracted data. Results: Nineteen PROMS had cross-culturally adapted and translated language versions. The KOOS, WOMAC, ACL-RSL, FAAM, ATRS, HOOS, OHS, MOXFQ and OKS were available in over 10 different language versions. Turkish, Dutch, German, Chinese and French were the most common languages, with each language having more than 10 PROMs with psychometric properties supporting their use. The WOMAC and KOOS were both available in 10 languages and had all three psychometric properties of reliability, validity, and responsiveness supporting their use. Conclusion: Nineteen of the 20 recommended instruments were available in multiple languages. The PROM most frequently cross-culturally adapted and translated were the KOOS and WOMAC. PROMs were most frequently cross-culturally adapted and translated into Turkish. International researchers and clinicians may use this information to more consistently implement PROMs with the most appropriate psychometric evidence available to support their use. Level of evidence: 3a.

Thiram, an inhibitor of 11ß-hydroxysteroid dehydrogenase type 2, enhances the inhibitory effects of hydrocortisone in the treatment of osteosarcoma through Wnt/ß-catenin pathway.

BACKGROUND: The anti-osteosarcoma effects of hydrocortisone and thiram, an inhibitor of type 2 11ß-hydroxysteroid dehydrogenase (11HSD2), have not been reported. The purpose of this study was to investigate the effects of hydrocortisone alone or the combination of hydrocortisone with thiram on osteosarcoma and the molecular mechanism, and determine whether they can be as new therapeutic agents for osteosarcoma. METHODS: Normal bone cells and osteosarcoma cells were treated with hydrocortisone or thiram alone or in combination. The cell proliferation, migration, cell cycle and apoptosis were detected by using CCK8 assay, wound healing assay, and flow cytometry, respectively. An osteosarcoma mouse model was established. The effect of drugs on osteosarcoma in vivo was assessed by measuring tumor volume. Transcriptome sequencing, bioinformatics analysis, RT-qPCR, Western blotting (WB), enzymelinked immunosorbent assay (ELISA) and siRNA transfection were performed to determine the molecular mechanisms. RESULTS: Hydrocortisone inhibited the proliferation and migration, and induced apoptosis and cell cycle arrest of osteosarcoma cells in vitro. Hydrocortisone also reduced the volume of osteosarcoma in mice in vivo. Mechanistically, hydrocortisone decreased the levels of Wnt/ß-catenin pathway-associated proteins, and induced the expression of glucocorticoid receptor α (GCR), CCAAT enhancer-binding protein ß (C/EBP-beta) and 11HSD2, resulting in a hydrocortisone resistance loop. Thiram inhibited the activity of the 11HSD2 enzyme, the combination of thiram and hydrocortisone further enhanced the inhibition of osteosarcoma through Wnt/ß-catenin pathway. CONCLUSIONS: Hydrocortisone inhibits osteosarcoma through the Wnt/ß-catenin pathway. Thiram inhibits 11HSD2 enzyme activity, reducing hydrocortisone inactivation and promoting the effect of hydrocortisone through the same pathway.

Yellow catfish RIO kinases (RIOKs) negatively regulate fish interferon-mediated antiviral response.

In mammals, right open reading frame kinases (RIOKs) are initially reported to participate in cancer cell proliferation, apoptosis, migration and invasion, and recently they have been related to host immune response. Little is known about the homologs of RIOKs in fish. In the current study, we cloned three homologous genes of RIOK family in yellow catfish (Pelteobagrus fulvidraco), termed Pfriok1, Pfriok2 and Pfriok3. Pfriok1, Pfriok2 and Pfriok3 were constitutively expressed at relatively high levels in yellow catfish tissues, and their mRNA levels were not changed under viral infection. Individual overexpression of PfRIOK1, PfRIOK2 and PfRIOK3 attenuated fish interferon (IFN) response, thereby promoting viral replication in fish cells. Mechanistically, yellow catfish RIOK proteins downregulated fish IFN response through attenuating TBK1 protein levels in cytoplasm. Our findings suggest that yellow catfish RIOK1, RIOK2 and RIOK3 are involved in downregulating fish IFN antiviral response.

[Application characteristics of Qugu (CV 2) in ancient and modern literature].

To summarize and analyze the clinical application characteristics of Qugu (CV 2) in ancient and modern literature based on data mining technology. The Chinese Medical Code (the 5th edition) was taken as the retrieval source of ancient literature, while the CNKI, Wanfang, and VIP databases were taken as the retrieval source of modern literature. The indications of Qugu (CV 2) used alone or with compatible acupoints, compatible acupoints, acupuncture-moxibustion manipulation, etc., were systematically sorted out. As a result, a total of 140 articles of ancient literature were included. The common indications of Qugu (CV 2) used alone were urinary retention, profuse vaginal discharge and hernia. The common indications of Qugu (CV 2) used with compatible acupoints were profuse vaginal discharge, stranguria and hernia. Sixty-four acupoints were concurrently used with Qugu (CV 2), Qugu (CV 2) was mainly compatible with acupoints of conception vessel, bladder meridian and liver meridian, and the high-frequency acupoints included Zhongji (CV 3), Guanyuan (CV 4) and Sanyinjiao (SP 6); five-shu points were the most used special acupoints, and moxibustion therapy was often used. A total of 73 modern articles were included. The common indications of Qugu (CV 2) used alone were urinary retention, erectile dysfunction and chronic prostatitis; the common indications of Qugu (CV 2) used with compatible scupoints were urinary retention, erectile dysfunction and prostatic hyperplasia. Thirty-six acupoints were concurrently used with Qugu (CV 2), Qugu (CV 2) was mainly compatible with acupoints of conception vessel, kidney meridian and spleen meridian, and the high-frequency acupoints included Zhongji (CV 3), Guanyuan (CV 4) and Zusanli (ST 36); front-mu points were the most used special acupoints, and acupuncture therapy was often used. Qugu (CV 2) treats a wide range of diseases in ancient times, the distant treatment effectiveness of acupoints is emphasized; and it mainly treats local diseases in modern times, the nearby treatment effectiveness of acupoints is emphasized.

Gastric cancer stem cell-derived exosomes promoted tobacco smoke-triggered development of gastric cancer by inducing the expression of circ670.

As one of the most common malignant cancers in the world, gastric cancer is caused by mang factors among which tobacco smoke is an important risk factor. Gastric cancer stem cells (GCSCs) and the derived exosomes play a key role in the occurrence and development of gastric cancer, and exosomal circRNA is considered as a new regulatory factor in the development of gastric cancer. However, it is unclear whether tobacco smoke can affect exosomes and their transport circRNAs to promote the development of gastric cancer. Herein, we provided a new insight into tobacco smoke promoting the progression of gastric cancer. In the present study, we demonstrated that tobacco smoke-induced exosomes promoted the spheroidizing ability, stemness genes expression, and epithelial-mesenchymal transition (EMT) process of GCSCs. We further found that hsa-circRNA-000670 (circ670) was up-regulated in tissues of gastric cancer patients with smoking history, tobacco smoke-induced GCSCs, and their exosomes. Functional assays have shown that circ670 knockdown inhibited the stemness and EMT process of GCSCs, whereas circ670 overexpression appeared to have an opposite effect. Our findings indicated that exosomal circ670 promotes the development of tobacco smoke-induced gastric cancer, which may provide insight into the mechanism of tobacco smoke promoting the progression of gastric cancer.

Construction and validation of prognostic prediction established on N6-methyladenosine related genes in cervical squamous cell carcinoma.

Background: Cervical cancer (CESC) is the second most common cancer death in middle-aged women. The N6-methyladenosine (m6A) plays an essential role in the epitranscriptomics of cancer and affects immune cell infiltration. Our study used The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data to construct and validate prognostic prediction established on m6A-related genes in CESC. Methods: We gained gene expression and clinical characteristics from TCGA and GEO. After differentially expression analysis of the m6A-related genes, we identified eight genes of CESC development. Next, we executed consensus clustering to analyze CESC types established on the differential expression of the m6A-related genes and found different subtypes significantly correlate with survival prognosis, immune microenvironment, and PD-L1 expression. Then, based on Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis, a five-gene (IGF2BP1, IGF2BP2, HNRNPA2B1, YTHDF1, RBM15) predictive model was built in the TCGA training cohort. Finally, we checked the predictive model with survival analysis and receiver operating characteristic (ROC) curve both in the training cohort (TCGA) and in the validation cohort (GSE44001). We found the expression and variation of the five genes significantly correlate with immune cell infiltration. Results: The CESC could be divided into subtypes according to eight expression m6A-related genes. Different subtypes are related to various immune cells, immune scores, and the expression of the PD-L1. We develop a risk prediction model: risk score = (0.023558929) * Exp IGF2BP1 + (0.021148829) * Exp IGF2BP2 + (0.045035491) * Exp HNRNPA2B1 + (-0.106566550) * Exp YTHDF1 + (-0.001037932) * Exp RBM15. Moreover, different m6A-related genes significantly correlated with immune cells. Conclusions: The m6A-related genes risk prediction model plays an essential role in predicting CESC patients. The m6A-related genes affected the immune cell infiltration in CESC. These results suggest that the expression of m6A-related genes may influence the immune therapy of CESC and be the potential therapeutic target.